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Showing papers by "University of British Columbia published in 2004"


Journal ArticleDOI
TL;DR: This paper presents a method for extracting distinctive invariant features from images that can be used to perform reliable matching between different views of an object or scene and can robustly identify objects among clutter and occlusion while achieving near real-time performance.
Abstract: This paper presents a method for extracting distinctive invariant features from images that can be used to perform reliable matching between different views of an object or scene. The features are invariant to image scale and rotation, and are shown to provide robust matching across a substantial range of affine distortion, change in 3D viewpoint, addition of noise, and change in illumination. The features are highly distinctive, in the sense that a single feature can be correctly matched with high probability against a large database of features from many images. This paper also describes an approach to using these features for object recognition. The recognition proceeds by matching individual features to a database of features from known objects using a fast nearest-neighbor algorithm, followed by a Hough transform to identify clusters belonging to a single object, and finally performing verification through least-squares solution for consistent pose parameters. This approach to recognition can robustly identify objects among clutter and occlusion while achieving near real-time performance.

46,906 citations


Journal ArticleDOI
TL;DR: When given with prednisone, treatment with docetaxel every three weeks led to superior survival and improved rates of response in terms of pain, serum PSA level, and quality of life, as compared with mitoxantrone plusprednisone.
Abstract: As compared with the men in the mitoxantrone group, men in the group given docetaxel every three weeks had a hazard ratio for death of 0.76 (95 percent confidence interval, 0.62 to 0.94; P = 0.009 by the stratified log-rank test) and those given weekly docetaxel had a hazard ratio for death of 0.91 (95 percent confidence interval, 0.75 to 1.11; P=0.36). The median survival was 16.5 months in the mitoxantrone group, 18.9 months in the group given docetaxel every 3 weeks, and 17.4 months in the group given weekly docetaxel. Among these three groups, 32 percent, 45 percent, and 48 percent of men, respectively, had at least a 50 percent decrease in the serum PSA level (P<0.001 for both comparisons with mitoxantrone); 22 percent, 35 percent (P=0.01), and 31 percent (P=0.08) had predefined reductions in pain; and 13 percent, 22 percent (P=0.009), and 23 percent (P=0.005) had improvements in the quality of life. Adverse events were also more common in the groups that received docetaxel. conclusions When given with prednisone, treatment with docetaxel every three weeks led to superior survival and improved rates of response in terms of pain, serum PSA level, and quality of life, as compared with mitoxantrone plus prednisone.

5,264 citations


Journal ArticleDOI
TL;DR: This framework is used to discuss why the metacommunity concept is useful in modifying existing ecological thinking and illustrate this with a number of both theoretical and empirical examples.
Abstract: The metacommunity concept is an important way to think about linkages between different spatial scales in ecology. Here we review current understanding about this concept. We first investigate issues related to its definition as a set of local communities that are linked by dispersal of multiple potentially interacting species. We then identify four paradigms for metacommunities: the patch-dynamic view, the species-sorting view, the mass effects view and the neutral view, that each emphasizes different processes of potential importance in metacommunities. These have somewhat distinct intellectual histories and we discuss elements related to their potential future synthesis. We then use this framework to discuss why the concept is useful in modifying existing ecological thinking and illustrate this with a number of both theoretical and empirical examples. As ecologists strive to understand increasingly complex mechanisms and strive to work across multiple scales of spatio-temporal organization, concepts like the metacommunity can provide important insights that frequently contrast with those that would be obtained with more conventional approaches based on local communities alone.

4,266 citations


Journal ArticleDOI
19 Mar 2004-Science
TL;DR: There is considerable interest in exploiting the advantages of DDS for in vivo delivery of new drugs derived from proteomics or genomics research and for their use in ligand-targeted therapeutics.
Abstract: Drug delivery systems (DDS) such as lipid- or polymer-based nanoparticles can be designed to improve the pharmacological and therapeutic properties of drugs administered parenterally. Many of the early problems that hindered the clinical applications of particulate DDS have been overcome, with several DDS formulations of anticancer and antifungal drugs now approved for clinical use. Furthermore, there is considerable interest in exploiting the advantages of DDS for in vivo delivery of new drugs derived from proteomics or genomics research and for their use in ligand-targeted therapeutics.

4,162 citations


Journal ArticleDOI
TL;DR: Progression of COPD is associated with the accumulation of inflammatory mucous exudates in the lumen and infiltration of the wall by innate and adaptive inflammatory immune cells that form lymphoid follicles, coupled to a repair or remodeling process that thickens the walls of these airways.
Abstract: Background Chronic obstructive pulmonary disease (COPD) is a major public health problem associated with long-term exposure to toxic gases and particles. We examined the evolution of the pathological effects of airway obstruction in patients with COPD. Methods The small airways were assessed in surgically resected lung tissue from 159 patients — 39 with stage 0 (at risk), 39 with stage 1, 22 with stage 2, 16 with stage 3, and 43 with stage 4 (very severe) COPD, according to the classification of the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Results The progression of COPD was strongly associated with an increase in the volume of tissue in the wall (P<0.001) and the accumulation of inflammatory mucous exudates in the lumen (P<0.001) of the small airways. The percentage of the airways that contained polymorphonuclear neutrophils (P<0.001), macrophages (P<0.001), CD4 cells (P=0.02), CD8 cells (P=0.038), B cells (P<0.001), and lymphoid aggregates containing follicles (P=0.003) and the abs...

3,401 citations


Journal Article
TL;DR: The second revision of the ILAR Taskforce on Classification of Childhood Arthritis (ILAR-JIA) was presented at the 2001 ILAR Workshop on Rheumatology as discussed by the authors.
Abstract: The primary aim of the International League of Associations for Rheumatology (ILAR) proposals for classification of juvenile idiopathic arthritis (JIA) is to delineate, for research purposes, relatively homogeneous, mutually exclusive categories of idiopathic childhood arthritis based on predominant clinical and laboratory features. As part of a continuing review process, the ILAR Taskforce on Classification of Childhood Arthritis met in Edmonton in 2001 to discuss modifications to the proposed JIA classification. Since the publication of the first revision of the original classification 1 , a number of descriptive studies using the new classification have been reported 2-11. The aims of this communication are 2-fold: to outline modifications to the revised classification proposed as a result of the Edmonton meeting, and to correct misconceptions highlighted by the published studies concerning the clinical use of the classification. The Edmonton Revision The changes embodied in the second revision of the classification are as follows: 1. Clarification of the definitions of each category. 2. Improvement in the congruity between inclusion and exclusion criteria. 3. Removal of the requirement that a dermatologist make the diagnosis of psoriasis. 4. Removal of the requirement that there be medical confirmation of HLA-B27 associated disease in a relative. 5. Reduction in the age for criterion " 3 " of enthesitis related arthritis, and exclusion " b " from 8 years to 6 years of age. 6. Improvement in the consistency of the structure. The impracticality of the requirement that a diagnosis of psoriasis be made by a dermatologist was recognized, and this requirement was modified so that the diagnosis of psori-asis could be made by a physician (not necessarily a dermatologist). Similarly, it is no longer required that there be medical confirmation of an HLA-B27 associated disease in a relative as contained in exclusion " c. " It is evident that it is very difficult to obtain a reliable history of psoriasis or an HLA-B27 associated disease in a second-degree relative. Therefore, a history of importance to the application of the criteria is restricted to the patient or a first-degree relative (parents or siblings) only. The study of Murray, et al 8 indicated that the HLA-B27 association is important in boys over the age of 6 years at onset of arthritis, and this age was substituted for 8 years in exclusion " b. " Discrepancies between inclusion and exclusion criteria were resolved, and the exclusions were identified by the letters …

3,201 citations


Journal ArticleDOI
18 Nov 2004-Neuron
TL;DR: High-resolution recombination mapping and candidate gene sequencing in 46 families found six disease-segregating mutations in a gene encoding a large, multifunctional protein, LRRK2 (leucine-rich repeat kinase 2), which may be central to the pathogenesis of several major neurodegenerative disorders associated with parkinsonism.

2,757 citations


Journal ArticleDOI
TL;DR: The present report meta-analyzes more than 300 empirical articles describing a relationship between psychological stress and parameters of the immune system in human participants to find that physical vulnerability as a function of age or disease also increased vulnerability to immune change during stressors.
Abstract: The present report meta-analyzes more than 300 empirical articles describing a relationship between psychological stress and parameters of the immune system in human participants. Acute stressors (lasting minutes) were associated with potentially adaptive upregulation of some parameters of natural immunity and downregulation of some functions of specific immunity. Brief naturalistic stressors (such as exams) tended to suppress cellular immunity while preserving humoral immunity. Chronic stressors were associated with suppression of both cellular and humoral measures. Effects of event sequences varied according to the kind of event (trauma vs. loss). Subjective reports of stress generally did not associate with immune change. In some cases, physical vulnerability as a function of age or disease also increased vulnerability to immune change during stressors.

2,756 citations


Journal ArticleDOI
TL;DR: A panel of four antibodies (ER, HER1, HER2, and cytokeratin 5/6) can accurately identify basal-like tumors using standard available clinical tools and shows high specificity.
Abstract: Purpose: Expression profiling studies classified breast carcinomas into estrogen receptor (ER)+/luminal, normal breast-like, HER2 overexpressing, and basal-like groups, with the latter two associated with poor outcomes. Currently, there exist clinical assays that identify ER+/luminal and HER2-overexpressing tumors, and we sought to develop a clinical assay for breast basal-like tumors. Experimental Design: To identify an immunohistochemical profile for breast basal-like tumors, we collected a series of known basal-like tumors and tested them for protein patterns that are characteristic of this subtype. Next, we examined the significance of these protein patterns using tissue microarrays and evaluated the prognostic significance of these findings. Results: Using a panel of 21 basal-like tumors, which was determined using gene expression profiles, we saw that this subtype was typically immunohistochemically negative for estrogen receptor and HER2 but positive for basal cytokeratins, HER1, and/or c-KIT. Using breast carcinoma tissue microarrays representing 930 patients with 17.4-year mean follow-up, basal cytokeratin expression was associated with low disease-specific survival. HER1 expression was observed in 54% of cases positive for basal cytokeratins ( versus 11% of negative cases) and was associated with poor survival independent of nodal status and size. c-KIT expression was more common in basal-like tumors than in other breast cancers but did not influence prognosis. Conclusions: A panel of four antibodies (ER, HER1, HER2, and cytokeratin 5/6) can accurately identify basal-like tumors using standard available clinical tools and shows high specificity. These studies show that many basal-like tumors express HER1, which suggests candidate drugs for evaluation in these patients.

2,562 citations


Journal ArticleDOI
Elise A. Feingold1, Peter J. Good1, Mark S. Guyer1, S. Kamholz1  +193 moreInstitutions (19)
22 Oct 2004-Science
TL;DR: The ENCyclopedia Of DNA Elements (ENCODE) Project is organized as an international consortium of computational and laboratory-based scientists working to develop and apply high-throughput approaches for detecting all sequence elements that confer biological function.
Abstract: The ENCyclopedia Of DNA Elements (ENCODE) Project aims to identify all functional elements in the human genome sequence. The pilot phase of the Project is focused on a specified 30 megabases (∼1%) of the human genome sequence and is organized as an international consortium of computational and laboratory-based scientists working to develop and apply high-throughput approaches for detecting all sequence elements that confer biological function. The results of this pilot phase will guide future efforts to analyze the entire human genome.

2,248 citations


Journal ArticleDOI
TL;DR: This work confirms that social capital is strongly linked to subjective well-being through many independent channels and in several different forms, both directly and through their impact on health.
Abstract: Large samples of data from the World Values Survey, the US Benchmark Survey and a comparable Canadian survey are used to estimate equations designed to explore the social context of subjective evaluations of well-being, of happiness, and of health. Social capital, as measured by the strength of family, neighbourhood, religious and community ties, is found to support both physical health and subjective well-being. Our new evidence confirms that social capital is strongly linked to subjective well-being through many independent channels and in several different forms. Marriage and family, ties to friends and neighbours, workplace ties, civic engagement (both individually and collectively), trustworthiness and trust: all appear independently and robustly related to happiness and life satisfaction, both directly and through their impact on health.

Journal ArticleDOI
TL;DR: A critical examination of the neglected biology of mitochondria is carried out and several surprising gaps in the state of the authors' knowledge about this important organelle are pointed out.
Abstract: Mitochondrial DNA (mtDNA) has been used to study molecular ecology and phylogeography for 25 years. Much important information has been gained in this way, but it is time to reflect on the biology of the mitochondrion itself and consider opportunities for evolutionary studies of the organelle itself and its ecology, biochemistry and physiology. This review has four sections. First, we review aspects of the natural history of mitochondria and their DNA to show that it is a unique molecule with specific characteristics that differ from nuclear DNA. We do not attempt to cover the plethora of differences between mitochondrial and nuclear DNA; rather we spotlight differences that can cause significant bias when inferring demographic properties of populations and/or the evolutionary history of species. We focus on recombination, effective population size and mutation rate. Second, we explore some of the difficulties in interpreting phylogeographical data from mtDNA data alone and suggest a broader use of multiple nuclear markers. We argue that mtDNA is not a sufficient marker for phylogeographical studies if the focus of the investigation is the species and not the organelle. We focus on the potential bias caused by introgression. Third, we show that it is not safe to assume a priori that mtDNA evolves as a strictly neutral marker because both direct and indirect selection influence mitochondria. We outline some of the statistical tests of neutrality that can, and should, be applied to mtDNA sequence data prior to making any global statements concerning the history of the organism. We conclude with a critical examination of the neglected biology of mitochondria and point out several surprising gaps in the state of our knowledge about this important organelle. Here we limelight mitochondrial ecology, sexually antagonistic selection, life-history evolution including ageing and disease, and the evolution of mitochondrial inheritance.

Journal ArticleDOI
TL;DR: Patients with fistulizing Crohn's disease who have a response to induction therapy with inflIXimab have an increased likelihood of a sustained response over a 54-week period if infliximab treatment is continued every 8 weeks.
Abstract: BACKGROUND: Infliximab, a monoclonal antibody against tumor necrosis factor, is an effective maintenance therapy for patients with Crohn's disease without fistulas. It is not known whether infliximab is an effective maintenance therapy for patients with fistulas. METHODS: We performed a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the efficacy of infliximab maintenance therapy in 306 adult patients with Crohn's disease and one or more draining abdominal or perianal fistulas of at least three months' duration. Patients received 5 mg of infliximab per kilogram of body weight intravenously on weeks 0, 2, and 6. A total of 195 patients who had a response at weeks 10 and 14 and 87 patients who had no response were then randomly assigned to receive placebo or 5 mg of infliximab per kilogram every eight weeks and to be followed to week 54. The primary analysis was the time to the loss of response among patients who had a response at week 14 and underwent randomization. RESULTS: The time to loss of response was significantly longer for patients who received infliximab maintenance therapy than for those who received placebo maintenance (more than 40 weeks vs. 14 weeks, P<0.001). At week 54, 19 percent of patients in the placebo maintenance group had a complete absence of draining fistulas, as compared with 36 percent of patients in the infliximab maintenance group (P=0.009). CONCLUSIONS: Patients with fistulizing Crohn's disease who have a response to induction therapy with infliximab have an increased likelihood of a sustained response over a 54-week period if infliximab treatment is continued every 8 weeks.

Journal ArticleDOI
01 Apr 2004-Nature
TL;DR: This first comprehensive analysis of the genome sequence of the Brown Norway (BN) rat strain is reported, which is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution.
Abstract: The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.

Journal ArticleDOI
01 Oct 2004-Science
TL;DR: The 34 million-base-pair draft nuclear genome of the marine diatom Thalassiosira pseudonana and its 129 thousand-base pair plastid and 44 thousand base-pair mitochondrial genomes were reported in this article.
Abstract: Diatoms are unicellular algae with plastids acquired by secondary endosymbiosis. They are responsible for approximately 20% of global carbon fixation. We report the 34 million-base pair draft nuclear genome of the marine diatom Thalassiosira pseudonana and its 129 thousand-base pair plastid and 44 thousand-base pair mitochondrial genomes. Sequence and optical restriction mapping revealed 24 diploid nuclear chromosomes. We identified novel genes for silicic acid transport and formation of silica-based cell walls, high-affinity iron uptake, biosynthetic enzymes for several types of polyunsaturated fatty acids, use of a range of nitrogenous compounds, and a complete urea cycle, all attributes that allow diatoms to prosper in aquatic environments.

Journal ArticleDOI
TL;DR: Land-use mix had the strongest association with obesity, and relationships among urban form, walk distance, and time in a car were stronger among white than black cohorts, while relationships among the built environment, travel patterns, and weight may vary across gender and ethnicity.

Journal ArticleDOI
01 Jul 2004-Thorax
TL;DR: Reduced lung function is associated with increased levels of systemic inflammatory markers which may have important pathophysiological and therapeutic implications for subjects with stable COPD.
Abstract: Background: Individuals with chronic obstructive pulmonary disease (COPD) are at increased risk of cardiovascular diseases, osteoporosis, and muscle wasting. Systemic inflammation may be involved in the pathogenesis of these disorders. A study was undertaken to determine whether systemic inflammation is present in stable COPD. Methods: A systematic review was conducted of studies which reported on the relationship between COPD, forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC), and levels of various systemic inflammatory markers: C-reactive protein (CRP), fibrinogen, leucocytes, tumour necrosis factor-a (TNF-a), and interleukins 6 and 8. Where possible the results were pooled together to produce a summary estimate using a random or fixed effects model. Results: Fourteen original studies were identified. Overall, the standardised mean difference in the CRP level between COPD and control subjects was 0.53 units (95% confidence interval (CI) 0.34 to 0.72). The standardised mean difference in the fibrinogen level was 0.47 units (95% CI 0.29 to 0.65). Circulating leucocytes were also higher in COPD than in control subjects (standardised mean difference 0.44 units (95% CI 0.20 to 0.67)), as were serum TNF-a levels (standardised mean difference 0.59 units (95% CI 0.29 to 0.89)). Conclusions: Reduced lung function is associated with increased levels of systemic inflammatory markers which may have important pathophysiological and therapeutic implications for subjects with stable COPD.

Journal ArticleDOI
TL;DR: The paper summarizes the capabilities of the modeling system with respect to evaluating how fisheries and the environment impact ecosystems and presents an overview of the computational aspects of the Ecopath, Ecosim and Ecospace modules as they are implemented in the most recent software version.

Journal ArticleDOI
TL;DR: In this article, the authors studied the effect of more than 15 million messages posted on Yahoo! Finance and Raging Bull about the 45 companies in the Dow Jones Industrial Average and Dow Jones Internet Index Bullishness was measured using computational linguistics methods.
Abstract: Financial press reports claim that Internet stock message boards can move markets We study the effect of more than 15 million messages posted on Yahoo! Finance and Raging Bull about the 45 companies in the Dow Jones Industrial Average and the Dow Jones Internet Index Bullishness is measured using computational linguistics methods Wall Street Journal news stories are used as controls We find that stock messages help predict market volatility Their effect on stock returns is statistically significant but economically small Consistent with Harris and Raviv (1993), disagreement among the posted messages is associated with increased trading volume MANY PEOPLE ARE DEVOTING a considerable amount of time and effort creating and reading the messages posted on Internet stock message boards News stories report that the message boards are having a significant impact on financial markets The Securities and Exchange Commission has prosecuted people for Internet messages All this attention to Internet stock messages caused us to wonder whether these messages actually contain financially relevant information 1 We consider three specific issues Does the number of messages posted or the bullishness of these messages help to predict returns? Is disagreement among the messages associated with more trades? Does the level of message posting or the bullishness of the messages help to predict volatility? The first issue is, does the level of message activity or the bullishness of the messages successfully predict subsequent stock returns? This is the natural starting place because a very high proportion of the messages contain explicit assertions that the particular stock is either a good buy or a bad buy Of course, there are a great many previous empirical studies showing how hard it is to predict stock returns by enough to cover transactions costs We find that there is evidence of a small degree of negative predictability even after controlling for bid‐ask bounce When many messages are posted on a given day, there ∗ Both authors are at the Sauder School of Business, University of British Columbia We would

Journal ArticleDOI
TL;DR: In this paper, the authors further develop their understanding of this methodological alternative by elaborating on the objective and mechanisms of its analytic processes and by expanding their consideration of its interpretive products.
Abstract: The past decade has witnessed remarkable evolution within qualitative health research as scholars have moved beyond initial adherence to the specific methods of phenomenology, grounded theory, and ethnography to develop methods more responsive to the experience-based questions of interest to a practice-based discipline. Interpretive description (Thorne, Reimer Kirkham, & MacDonald-Emes, 1997) is an inductive analytic approaches designed to create ways of understanding clinical phenomena that yield applications implications. In this article, we further develop our understanding of this methodological alternative by elaborating on the objective and mechanisms of its analytic processes and by expanding our consideration of its interpretive products.

Journal ArticleDOI
08 Apr 2004-Nature
TL;DR: In this article, it was shown that spatial structure reduces the proportion of cooperators for a wide range of parameters in unstructured snowdrift games, and in particular, spatial structure eliminates cooperation if the cost-to-benefit ratio of cooperation is high.
Abstract: Understanding the emergence of cooperation is a fundamental problem in evolutionary biology. Evolutionary game theory has become a powerful framework with which to investigate this problem. Two simple games have attracted most attention in theoretical and experimental studies: the Prisoner's Dilemma and the snowdrift game (also known as the hawk-dove or chicken game). In the Prisoner's Dilemma, the non-cooperative state is evolutionarily stable, which has inspired numerous investigations of suitable extensions that enable cooperative behaviour to persist. In particular, on the basis of spatial extensions of the Prisoner's Dilemma, it is widely accepted that spatial structure promotes the evolution of cooperation. Here we show that no such general predictions can be made for the effects of spatial structure in the snowdrift game. In unstructured snowdrift games, intermediate levels of cooperation persist. Unexpectedly, spatial structure reduces the proportion of cooperators for a wide range of parameters. In particular, spatial structure eliminates cooperation if the cost-to-benefit ratio of cooperation is high. Our results caution against the common belief that spatial structure is necessarily beneficial for cooperative behaviour.

Journal ArticleDOI
16 Jul 2004-Science
TL;DR: The geological, geochemical, and biological processes that contributed to the rise of the dinoflagellates, coccolithophores, and diatoms all contain plastids derived from an ancestral red alga by secondary symbiosis are examined.
Abstract: The community structure and ecological function of contemporary marine ecosystems are critically dependent on eukaryotic phytoplankton. Although numerically inferior to cyanobacteria, these organisms are responsible for the majority of the flux of organic matter to higher trophic levels and the ocean interior. Photosynthetic eukaryotes evolved more than 1.5 billion years ago in the Proterozoic oceans. However, it was not until the Mesozoic Era (251 to 65 million years ago) that the three principal phytoplankton clades that would come to dominate the modern seas rose to ecological prominence. In contrast to their pioneering predecessors, the dinoflagellates, coccolithophores, and diatoms all contain plastids derived from an ancestral red alga by secondary symbiosis. Here we examine the geological, geochemical, and biological processes that contributed to the rise of these three, distantly related, phytoplankton groups.

Journal ArticleDOI
TL;DR: The length of survival among patients with follicular lymphoma correlates with the molecular features of nonmalignant immune cells present in the tumor at diagnosis.
Abstract: background Patients with follicular lymphoma may survive for periods of less than 1 year to more than 20 years after diagnosis. We used gene-expression profiles of tumor-biopsy specimens obtained at diagnosis to develop a molecular predictor of the length of survival. methods Gene-expression profiling was performed on 191 biopsy specimens obtained from patients with untreated follicular lymphoma. Supervised methods were used to discover expression patterns associated with the length of survival in a training set of 95 specimens. A molecular predictor of survival was constructed from these genes and validated in an independent test set of 96 specimens. results Individual genes that predicted the length of survival were grouped into gene-expression signatures on the basis of their expression in the training set, and two such signatures were used to construct a survival predictor. The two signatures allowed patients with specimens in the test set to be divided into four quartiles with widely disparate median lengths of survival (13.6, 11.1, 10.8, and 3.9 years), independently of clinical prognostic variables. Flow cytometry showed that these signatures reflected gene expression by nonmalignant tumor-infiltrating immune cells. conclusions The length of survival among patients with follicular lymphoma correlates with the molecular features of nonmalignant immune cells present in the tumor at diagnosis.

Journal ArticleDOI
TL;DR: In this article, the authors examine the theory and practice of sustainable development in the context of three criticisms (it is vague, attracts hypocrites and fosters delusions), and argue for an approach to sustainability that is integrative, is action-oriented, goes beyond technical fixes, incorporates a recognition of the social construction of sustainable Development, and engages local communities in new ways.

Journal ArticleDOI
TL;DR: Current levels of air pollution have chronic, adverse effects on lung development in children from the age of 10 to 18 years, leading to clinically significant deficits in attained FEV as children reach adulthood.
Abstract: background Whether exposure to air pollution adversely affects the growth of lung function during the period of rapid lung development that occurs between the ages of 10 and 18 years is unknown. methods In this prospective study, we recruited 1759 children (average age, 10 years) from schools in 12 southern California communities and measured lung function annually for eight years. The rate of attrition was approximately 10 percent per year. The communities represented a wide range of ambient exposures to ozone, acid vapor, nitrogen dioxide, and particulate matter. Linear regression was used to examine the relationship of air pollution to the forced expiratory volume in one second (FEV 1 ) and other spirometric measures. results Over the eight-year period, deficits in the growth of FEV 1 were associated with exposure to nitrogen dioxide (P=0.005), acid vapor (P=0.004), particulate matter with an aerodynamic diameter of less than 2.5 µm (PM 2.5 ) (P=0.04), and elemental carbon (P=0.007), even after adjustment for several potential confounders and effect modifiers. Associations were also observed for other spirometric measures. Exposure to pollutants was associated with clinically and statistically significant deficits in the FEV 1 attained at the age of 18 years. For example, the estimated proportion of 18-year-old subjects with a low FEV 1 (defined as a ratio of observed to expected FEV 1 of less than 80 percent) was 4.9 times as great at the highest level of exposure to PM 2.5 as at the lowest level of exposure (7.9 percent vs. 1.6 percent, P=0.002). conclusions The results of this study indicate that current levels of air pollution have chronic, adverse effects on lung development in children from the age of 10 to 18 years, leading to clinically significant deficits in attained FEV 1 as children reach adulthood.

Journal ArticleDOI
TL;DR: The purpose and mechanisms of the leading algorithms, with a particular emphasis on metazoan sequence analysis, are introduced and key issues that users should take into consideration in interpreting the results are identified.
Abstract: The compilation of multiple metazoan genome sequences and the deluge of large-scale expression data have combined to motivate the maturation of bioinformatics methods for the analysis of sequences that regulate gene transcription. Historically, these bioinformatics methods have been plagued by poor predictive specificity, but new bioinformatics algorithms that accelerate the identification of regulatory regions are drawing disgruntled users back to their keyboards. However, these new approaches and software are not without problems. Here, we introduce the purpose and mechanisms of the leading algorithms, with a particular emphasis on metazoan sequence analysis. We identify key issues that users should take into consideration in interpreting the results and provide an online training example to help researchers who wish to test online tools before taking an independent foray into the bioinformatics of transcription regulation.

Journal ArticleDOI
TL;DR: Among patients infected with both HIV and HCV, the combination of peginterferon alfa-2a plus ribavirin was significantly more effective than either interferonalfa- 2a plus Ribavirin or pegin terferonAlfa-3a monotherapy.
Abstract: Background Hepatitis C virus (HCV) infection is highly prevalent and is associated with substantial morbidity and mortality among persons infected with the human immunodeficiency virus (HIV). We compared the efficacy and safety of pegylated interferon alfa-2a (peginterferon alfa-2a) plus either ribavirin or placebo with those of interferon alfa-2a plus ribavirin for the treatment of chronic HCV infection in patients who were also infected with HIV. Methods A total of 868 persons who were infected with both HIV and HCV and who had not previously been treated with interferon or ribavirin were randomly assigned to receive one of three regimens: peginterferon alfa-2a (180 μg per week) plus ribavirin (800 mg per day), peginterferon alfa-2a plus placebo, or interferon alfa-2a (3 million IU three times a week) plus ribavirin. Patients were treated for 48 weeks and followed for an additional 24 weeks. The primary end point was a sustained virologic response (defined as a serum HCV RNA level below 50 IU per millil...

Book ChapterDOI
11 May 2004
TL;DR: This work introduces a vision system that is capable of learning, detecting and tracking the objects of interest, and interleaving Adaboost with mixture particle filters, a simple, yet powerful and fully automatic multiple object tracking system.
Abstract: The problem of tracking a varying number of non-rigid objects has two major difficulties. First, the observation models and target distributions can be highly non-linear and non-Gaussian. Second, the presence of a large, varying number of objects creates complex interactions with overlap and ambiguities. To surmount these difficulties, we introduce a vision system that is capable of learning, detecting and tracking the objects of interest. The system is demonstrated in the context of tracking hockey players using video sequences. Our approach combines the strengths of two successful algorithms: mixture particle filters and Adaboost. The mixture particle filter [17] is ideally suited to multi-target tracking as it assigns a mixture component to each player. The crucial design issues in mixture particle filters are the choice of the proposal distribution and the treatment of objects leaving and entering the scene. Here, we construct the proposal distribution using a mixture model that incorporates information from the dynamic models of each player and the detection hypotheses generated by Adaboost. The learned Adaboost proposal distribution allows us to quickly detect players entering the scene, while the filtering process enables us to keep track of the individual players. The result of interleaving Adaboost with mixture particle filters is a simple, yet powerful and fully automatic multiple object tracking system.

Journal ArticleDOI
TL;DR: The technology needed to diagnose and quantitate the individual small airway and emphysema phenotypes present in people with COPD is being developed, and should prove helpful in the assessment of therapeutic interventions designed to modify the progress of either phenotype.

Journal ArticleDOI
14 May 2004-Science
TL;DR: Using hippocampal slice preparations, it is shown that selectively blocking NMDARs that contain the NR2B subunit abolishes the induction of LTD but not LTP, demonstrating that distinct N MDAR subunits are critical factors that determine the polarity of synaptic plasticity.
Abstract: Activation of N-methyl-d-aspartate subtype glutamate receptors (NMDARs) is required for long-term potentiation (LTP) and long-term depression (LTD) of excitatory synaptic transmission at hippocampal CA1 synapses, the proposed cellular substrates of learning and memory. However, little is known about how activation of NMDARs leads to these two opposing forms of synaptic plasticity. Using hippocampal slice preparations, we showed that selectively blocking NMDARs that contain the NR2B subunit abolishes the induction of LTD but not LTP. In contrast, preferential inhibition of NR2A-containing NMDARs prevents the induction of LTP without affecting LTD production. These results demonstrate that distinct NMDAR subunits are critical factors that determine the polarity of synaptic plasticity.